Hypercholesterolemia is known to be one of the prime risk factors for ischemic cardiovascular disease, such as arteriosclerosis. Bile acid sequestrants have been used to treat this condition; they seem to be moderately effective but they must be consumed in large quantities, i.e. several grams at a time and they are not very palatable.
MEVACOR.RTM. (lovastatin), now commercially available, is one of a group of very active antihypercholesterolemic agents that function by limiting cholesterol biosynthesis by inhibiting the enzyme, HMG-CoA reductase. In addition to the natural fermentation products, mevastatin and lovastatin, there are a variety of semi-synthetic and totally synthetic analogs thereof.
The naturally occurring compounds and their semi-synthetic analogs have the following general structural formulae: ##STR2## wherein:
R.sup.3 is hydrogen, C.sub.1-5 alkyl or C.sub.1-5 alkyl substituted with a member of the group consisting of phenyl, dimethylamino, or acetylamino; and
R* is: ##STR3## wherein Q is ##STR4## R.sup.4 is H or OH; M is CHR.sup.5, is H or OH; and
R.sup.2 is hydrogen or methyl; and a, b, c, and d represent optional double bonds, especially where b and d represent double bonds or a, b, c, and d are all single bonds, provided that when a is a double bond, Q is ##STR5##
U.S. Pat. No. 4,444,784 discloses compounds of the above formula wherein R* is: ##STR6## wherein R' is H or CH.sub.3 and wherein amongst other groups R is phenyl or halophenyl where halo is chloro, fluoro, bromo or iodo. One compound 2, 4, F.sub.2 --C.sub.6 H.sub.3 CO.sub.2 -- is disclosed, but not prepared, in which the phenyl ring is ortho substituted.
Copending U.S. patent application Ser. No. 048,136 filed May 15, 1987, discloses compounds of the above formula wherein R* is: ##STR7## and R is CH.sub.2 OH or CO.sub.2 H and related alcoholic and carboxy derivatives and R.sup.1 amongst other groups is phenyl or phenyl substituted with X and Y where X and Y are selected from a broad range of groups defined in claim 1.